There is considerable interest in developing new quantitative imaging methods to monitor and predict breast cancer response to neoadjuvant chemotherapy, both prior to and as early as possible during the course of treatment. Diffuse optical spectroscopic imaging (DOSI) allows patients to be followed from baseline through treatment and surgery with a cost-effective, bedside, handheld scanning probe. In this work, we propose to significantly advance the development of harmonized DOSI technology platform and evaluate its performance in five clinical sites on up to 90 neoadjuvant chemotherapy patients. In preliminary patient studies, DOSI quantitative functional endpoints have been shown to be effective in predicting tumor response to chemotherapy within the first week of a two - four month treatment regimen. In the proposed work we will optimize and improve DOSI functionality, standardize clinical measurement and analysis procedures, and evaluate whether DOSI can be used with equivalent overall performance by different operators. Our long-term goal is to identify quantitative clinical endpoints that can be used to inform medical decisions on chemotherapy regimen, duration, and timing of surgery. These non-invasive endpoints are obtained rapidly with no risk/discomfort and could be used as surrogate markers of pathologic response, an established indicator of long-term survival. An archived database of breast cancer spectroscopic markers will be made available to the research community in order to further facilitate new technology development and enhance our understanding of breast cancer chemotherapy. Few technologies have bridged the gap between laboratory prototype and clinically disseminated cancer imaging system. We are now poised to make this transition by creating a standardized and validated DOSI platform, necessary next steps in the translational research process. Ultimately this work is expected to lead to a bedside optical imaging technology that can be used to improve patient outcome by maximizing therapeutic response, minimizing unnecessary toxicity, and optimizing clinical decision-making. PUBLIC HEALTH RELEVANCE: We propose to advance the development of a portable, bedside optical imaging technology capable of monitoring and predicting patient response to breast cancer neoadjuvant chemotherapy. The technology, Diffuse Optical Spectroscopic Imaging (DOSI), will be evaluated in a multi-site study designed to validate optical endpoints of clinical response.